Skip to content
New issue

Have a question about this project? Sign up for a free GitHub account to open an issue and contact its maintainers and the community.

Sign up for GitHub

By clicking “Sign up for GitHub”, you agree to our terms of service and privacy statement. We’ll occasionally send you account related emails.

Already on GitHub? Sign in to your account

Jump to bottom

Side chain clashes in docks. #415

Closed
primaryodors opened this issue Dec 23, 2023 · 5 comments · Fixed by #514
Closed

Side chain clashes in docks. #415

primaryodors opened this issue Dec 23, 2023 · 5 comments · Fixed by #514
Labels
bug Something isn't working. CRITICAL Something is very wrong. help wanted Extra attention is requested. high priority Above average priority.

Comments

@primaryodors
Copy link
Owner

primaryodors commented Dec 23, 2023 •
edited
Loading

Sometimes, the docker produces output in which residue side chains have been flexed into impossible positions clashing with other side chains of the protein.

TODO: Find an example.
@primaryodors primaryodors added bug Something isn't working. high priority Above average priority. labels Dec 23, 2023
@primaryodors
Copy link
Owner Author

http://primaryodors.net/viewer.php?view=dock&prot=OR51E2&odor=capric_acid&mode=active

Arg262 is clashing with Val195.

@primaryodors
Copy link
Owner Author

This seems to be happening in the FYG-motif active model, not in the dock. It may be wise to add a final step in all the active model predictors to flex any clashing side chains just enough to bring their clash energy below some set threshold.

@primaryodors
Copy link
Owner Author

This was addressed in #491 .

If the problem persists, this issue may be reopened.

@primaryodors primaryodors reopened this Dec 29, 2024
@primaryodors primaryodors added help wanted Extra attention is requested. CRITICAL Something is very wrong. labels Dec 29, 2024
@primaryodors
Copy link
Owner Author

Seems to happen pretty consistently between H104~Q158 with Z-3-hexenol (non-agonist) in OR10G7. There is no excuse for this.

image

If hexenol is a non agonist due to being energetically unfavorable in OR10G7, then the docker shouldn't output any poses. It should never produce any pose with such a serious clash between side chains.

primaryodors added a commit that referenced this issue Dec 30, 2024
@primaryodors
Stays flexions cause side chain clashes. #415
59f94c4
primaryodors added a commit that referenced this issue Dec 31, 2024
@primaryodors
Fix internal contacts in OR models. (#501)
53ab5f3 
* Models.

* Protonation functions.

* Stays flexions cause side chain clashes. #415

* Spacefill UI.
@primaryodors primaryodors linked a pull request Feb 5, 2025 that will close this issue
mclashables in bond rotations #415 #514
Merged
primaryodors added a commit that referenced this issue Feb 5, 2025
@primaryodors
mclashables in bond rotations #415 (#514)
c77ef1e 
* Constant to enable checking mclashes each rotation and forbidding rotation if clash is worse.

* Fewer flexions for performance.

* Atom::Z as const reference.

* Lennard Jones better performance.

* Fast math.

* Conjugated charge from Conjugation object.

* Code to revert drifts and BB points if interactions worsened.

* Loneliest point rewrite.

* Abhor vacuum function.

* Riglig feature i.e. ligand as rigid body.

* Crash fix.

* Pocket center from cavities.

* Addressed compiler warnings.

* Segfault fix.

* Caprylate unit test.

* Ensure mclashables are set.

* Increase stay-close atom enforcement.

* Global callbacks.
@primaryodors
Copy link
Owner Author

Reopen this issue if more side chain clashes are found, naming the receptor + ligand combination that exhibits clashes.

Sign up for free to join this conversation on GitHub. Already have an account? Sign in to comment
Assignees
No one assigned
Labels
bug Something isn't working. CRITICAL Something is very wrong. help wanted Extra attention is requested. high priority Above average priority.
Projects
None yet
Milestone
No milestone
Development

Successfully merging a pull request may close this issue.

mclashables in bond rotations #415 primaryodors/primarydock
1 participant
@primaryodors